Seasonal changes in immune function, health and disease are ubiquitous in humans, and contribute to annual patterns of mortality. The overall goal of the proposed research is to specify mechanisms by which endogenous and environmental factors control seasonal changes in the immune system of mammals. Analogies between photoperiodic control of the reproductive system and the immune system are critically examined at a formal level, and neural pathways are investigated at a mechanistic level. The point of departure for this work is the observation that exposure to short photoperiods alters several measures of immunity in Siberian hamsters; these changes occur entirely independently of the concurrent regression of the reproductive system. The formal properties and physiological substrates of the mechanism that perceives change in day length and communicates this information to the immune system remain unknown. These experiments will use in vivo and ex vivo measures of immune function to: (1) document the impact of natural changes in photoperiod on the immune system, (2) determine whether photoperiodic changes in immunity are dependent on pineal melatonin secretion and whether the duration of nocturnal melatonin secretion is the critical parameter for imparting seasonal information into the immune system, (3) identify the thalamic and hypothalamic melatonin target tissues that mediate the effects of photoperiod on the immune system, and (4) determine whether photoperiod-induced changes in sensitivity to inflammatory cytokine production participate in physiological and behavioral changes evident in the immune responses of mammals at different stages of their seasonal cycles.